What Can Prenatal Testing Reveal? — Chromosomal Abnormalities and Fetal Sex

What is NIPT?

In recent years, NIPT (Non-Invasive Prenatal Testing) has been gaining significant attention among expectant mothers.
NIPT analyzes fetal DNA fragments in the mother’s blood to screen for chromosomal abnormalities such as Down syndrome (trisomy 21) with high accuracy.

Compared to traditional prenatal testing, NIPT poses minimal risk to both mother and fetus. It can be performed from the 10th week of pregnancy and has rapidly spread as a new screening option.

This article answers the question: “What can NIPT detect?” We will explain its mechanism, detectable chromosomal abnormalities, whether sex determination is possible, accuracy, and important considerations.

Chromosomal Abnormalities Detectable by NIPT

1. Trisomy 21 (Down syndrome)
   The most common abnormality, caused by an extra 21st chromosome. Often associated with intellectual disability, characteristic facial features, and congenital heart disease.

• Prevalence: ~1 in 700
• Sensitivity: ≥99%
• Specificity: ≥99%
  (Source: Gil et al., 2015)

2. Trisomy 18 (Edwards syndrome)
   Caused by an extra 18th chromosome. Leads to severe growth restriction, heart defects, and usually results in fetal or neonatal death.

• Prevalence: ~1 in 5,000
• Sensitivity: 97–99%
• Specificity: ≥99%

3. Trisomy 13 (Patau syndrome)
   Caused by an extra 13th chromosome. Associated with severe brain and heart malformations, with very poor prognosis.

• Prevalence: ~1 in 10,000
• Sensitivity: 91–96%
• Specificity: ≥99%

4. Sex Chromosome Abnormalities (optional depending on facility)
   Examples include:

• Turner syndrome (45,X)
• Klinefelter syndrome (47,XXY)
• Jacob’s syndrome (47,XYY)

※ These do not always cause severe symptoms. Whether to test should be discussed with a doctor.

Can NIPT Determine Sex?

Yes. NIPT can identify fetal sex with high accuracy by detecting the presence of a Y chromosome in maternal blood.

• Y chromosome present → male
• No Y chromosome → female

However, in Japan, many facilities do not disclose fetal sex results, and NIPT is not offered solely for sex determination.

Mechanism and Accuracy of NIPT

• Principle: From the 10th week of pregnancy, a small fraction (~10%) of cell-free fetal DNA (cfDNA), derived from the placenta, circulates in maternal blood. NIPT extracts and analyzes this cfDNA using next-generation sequencing (NGS) to detect chromosomal imbalances.
• Accuracy: NIPT is a highly accurate screening test, but not a diagnostic test. A positive result requires confirmatory testing via amniocentesis or chorionic villus sampling.

Positive ≠ Diagnosis: False Positives and Negatives

• False positives: Caused by placental mosaicism or DNA abnormalities.
• False negatives: May occur due to insufficient fetal cfDNA concentration or rare abnormalities.
• Multiple pregnancies (twins, etc.): Lower accuracy, sometimes excluded.

NIPT in Japan: Testing Types and Conditions

1. Clinical Research Model (Certified Facilities)

• Target: Pregnant women ≥35 or those at high risk
• Cost: ~¥150,000–¥200,000
• Fetal sex and sex chromosome results: Generally not disclosed

2. Private Clinics (Non-certified, self-funded)

• Target: No age restrictions (available to women in their 20s)
• Cost: ~¥80,000–¥150,000
• Fetal sex and sex chromosome abnormalities: Sometimes disclosed

Benefits and Challenges of NIPT

Benefits

• High accuracy, non-invasive, minimal risk
• Available from early pregnancy (10 weeks onward)
• Enables early confirmatory testing if positive

Challenges / Ethical Issues

Importance of genetic counseling

Potential link to selective abortion → eugenics concerns

Handling sensitive information (sex selection, discrimination)

Expanding Scope of NIPT

With technological advances, some facilities now screen for microdeletion syndromes, such as:

1. 22q11.2 Deletion Syndrome (DiGeorge Syndrome)
   Associated with congenital heart disease, immune deficiency, and developmental delay.

• Prevalence: ~1 in 2,000–4,000
• Sensitivity/specificity: Varies; some studies report ≥90%

2. Other examples

• Cri-du-chat syndrome (5p deletion)
• 1p36 deletion syndrome
• Angelman syndrome / Prader-Willi syndrome (15q-related)

Key Considerations Before Testing

1. Timing: Most NIPT is performed at ≥10 weeks gestation.
2. Sample & turnaround time: ~10ml blood sample; results in ~1 week. Some clinics offer expedited options.
3. Pre- and post-test counseling: Essential to discuss testing goals and possible responses to a positive result with family and doctors.

Global Trends vs. Japan

• Overseas: Widely available in the US, UK, and other countries. In some regions, insurance covers part or all of the cost. Commercial labs offer expanded genetic testing.
• Japan: Still mainly self-funded; access and cost vary. Growth of non-certified clinics has raised concerns over inadequate counseling. The Japan Society of Obstetrics and Gynecology has revised guidelines to emphasize ethics and accurate information sharing.

Frequently Asked Questions (FAQ)

Q1. Does NIPT detect all fetal abnormalities?
→ No. It is a screening test. Positive results require confirmatory testing.

Q2. Is it meaningful for young women to take NIPT?
→ Yes. While risk increases with maternal age, younger women are not risk-free. Many in their 20s also seek reassurance through testing.

Q3. How are results delivered?
→ Typically via in-person or online consultation with a doctor. Solely mailing or emailing results may lead to insufficient explanation.

Conclusion: Understand NIPT Correctly, Choose Wisely

• NIPT is a high-accuracy screening, not a diagnosis
• Knowledge of chromosomal and sex chromosome abnormalities, as well as microdeletions, is essential
• Counseling with medical professionals is indispensable
• Clear testing goals and ethical considerations are necessary

Used appropriately, NIPT can serve as a reliable tool for reassurance and informed decision-making — setting a new standard for prenatal testing.